Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Hum Genet. 2001 Nov;69(5):936-50. Epub 2001 Sep 14.

Genomewide scans of complex human diseases: true linkage is hard to find.

Author information

  • 1Institute of Epidemiology, GSF [corrected] National Research Center for Environment and Health, Neuherberg, Germany. altmueller@gsf.de

Erratum in

  • Am J Hum Genet 2001 Dec;69(6):1413.

Abstract

Many "complex" human diseases, which involve multiple genetic and environmental determinants, have increased in incidence during the past 2 decades. During the same time period, considerable effort and expense have been expended in whole-genome screens aimed at detection of genetic loci contributing to the susceptibility to complex human diseases. However, the success of positional cloning attempts based on whole-genome screens has been limited, and many of the fundamental questions relating to the genetic epidemiology of complex human disease remain unanswered. Both to review the success of the positional cloning paradigm as applied to complex human disease and to investigate the characteristics of the whole-genome scans undertaken to date, we created a database of 101 studies of complex human disease, which were found by a systematic Medline search (current as of December 2000). We compared these studies, concerning 31 different human complex diseases, with regard to design, methods, and results. The "significance" categorizations proposed by Lander and Kruglyak were used as criteria for the "success" of a study. Most (66.3% [n=67]) of the studies did not show "significant" linkage when the criteria of Lander and Kruglyak (1995) were used, and the results of studies of the same disease were often inconsistent. Our analyses suggest that no single study design consistently produces more-significant results. Multivariate analysis suggests that the only factors independently associated with increased study success are (a) an increase in the number of individuals studied and (b) study of a sample drawn from only one ethnic group. Positional cloning based on whole-genome screens in complex human disease has proved more difficult than originally had been envisioned; detection of linkage and positional cloning of specific disease-susceptibility loci remains elusive.

Comment in

PMID:
11565063
[PubMed - indexed for MEDLINE]
PMCID:
PMC1274370
Free PMC Article

Images from this publication.See all images (3)Free text

Figure  1
Figure  2
Figure  3
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk